Age is the major risk factor for neurocognitive decline and dementia. Preventing and treating age-associated brain disorders will require elucidating the processes and mechanisms underlying normal brain aging and developing interventions that target such mechanisms. This project is based on the hypothesis that rapamycin retards brain aging by correcting age- associated aberrant DNA methylation regulation in the brain. The project tests one unique prediction of this hypothesis in aged mice treated with rapamycin compared with controls: Changes with age will be retarded by rapamycin in DNA methylations and the DNA methylation regulated genes important to synaptic and cognitive function in brain.